Introducing biocompatible and/or bioactive substances to a biologic system has its challenges. An ideal delivery would follow zero-order kinetics, such that the blood level after delivery of the biocompatible and/or bioactive substance remains constant. Current delivery systems, including porous polymers have been described but macroporous polymers have never been shown to offer zero-order release. Some porous polymers are strongly adhesive to the gastrointestinal mucus and cellular lining of the body, thereby limiting their use for local delivery to other sites. In addition, macroporous polymers have only been found to exhibit first-order kinetics. Early evidence using polymers of poly(lactide-co-glycolide) suggests that after 12 hours or so, there may be a near zero-order kinetics; however, release of protein was considered low. Using hollow microspheres of poly(lactide-co-glycolide), others have ultrasonically produced holes in the spheres, which, it was suggested may provide a means to releasing substances within its core.
With current microspheres, loading efficiencies of the current systems remains quite low because loading occurs after the polymer particles are formed, hence after they have polymerized.
In addition to the above issues and the low encapsulation efficiency currently found with said systems, there are further limitations with current microspheres that include particle size distribution, solvent removal, and bioactivity loss.
The invention described improves upon current systems and also overcomes challenges just described.